Balloon angioplasty has been very effective in treating stenosis, i.e., to open blocked vessels and restore normal levels of blood flow. However, although once a blocked vessel is opened, the treated vessel can restenose, i.e., reclose, shortly after the procedure. Thus, patients may have to undergo repeated angioplasty or even surgery.
Implantable stent prosthesis or stents are used to reduce restenosis after balloon angioplasty or other procedures using catheters. A stent in the form of a wire mesh tube props open an artery that has recently been cleared using angioplasty. A balloon expendable stent is collapsed to a small diameter, placed over an angioplasty balloon catheter and moved into the area of the blockage. When the balloon is inflated, the stent expands, locks in place and forms a scaffold to hold the artery open. A self-expandable stent is collapsed to a small diameter by placing in a sheath, and expands in the area of the blockage when the sheath surrounding the stent is removed. Usually, the stent stays in the artery permanently, holds it open, improves blood flow to the heart muscle and relieves symptoms. The stent procedure is fairly common, and various types of stents have been developed and actually used.
A variety of medical conditions have been treated by introducing an insertable medical device having a coating for release of a biologically active material. For example, various types of biologically active material-coated medical devices, such as stents, have been proposed for localized delivery of the biologically active material to a body lumen, such as to reduce the possibility of restenosis. See, e.g., U.S. Pat. No. 6,099,562 to Ding et al. However, it has been noted that, with existing coated medical devices, the release profile of a biologically active material may not be uniform along the entire length of the medical device.
For example, even if a biologically active material having a pharmacological effect is delivered to a body tissue, such effect may not result if the concentration of the biologically active material in the body tissue is below a certain concentration. Such concentration is referred to as the minimum effective concentration (Cmin) of the biologically active material in the body tissue. Each biologically active material has different Cmin. Cmin of a biologically active material also varies depending on the type of body tissue to which it is delivered. On the other hand, a biologically active material becomes toxic if its concentration is higher than a certain concentration. Such concentration is referred to as the maximum effective concentration Cmax. In addition, it is insufficient that the mean concentration of the biologically active material delivered through out the body tissue to be treated is greater than Cmin and smaller than Cmax. The concentration of the biologically active material at each and every area throughout the body tissue to be treated should be equal to or greater than Cmin but equal to or smaller than Cmax of the biologically active material. For instance, when a coated stent comprised of struts, such as the stent shown in FIG. 1, is used as a medical device for delivering a hydrophobic biologically active material, concentrations of the biologically active material may significantly differ between the regions of the tissue adjacent to the struts and the regions of the tissue farther from the struts. See Hwang et al., http://www.circulationaha.org (accepted in April 2001). Even if the mean concentration of the biologically active material in the tissue surrounding the stent is above Cmin of the biologically active material and at or under Cmax, the concentrations at certain regions of the tissue to be treated, which are farther from the struts, may not reach Cmin. Also, if the amount of the biologically active material in the coating is increased to achieve a concentration higher than Cmin at all regions of the tissue to be treated, then the concentrations at regions of the tissue adjacent to the struts may exceed the toxic levels, as explained below using the figures.
In FIG. 1, the coated stent 10 is placed in a blood vessel 15 having a vessel wall 12 to be treated. This vessel wall is surrounded by tissue 12a. The biologically active material coated on struts 13 of the stent 10 is released into the vessel wall 12 to be treated. FIG. 2 is a cross sectional view along line A of the stent 10 in FIG. 1. FIG. 2 also shows the concentration levels of the biologically active material in each area surrounding the struts 13 at a certain time after the insertion of the stent into the vessel 15. The area adjacent to the struts, i.e., the area between the struts 13 and line 16, has a concentration level at or below Cmax, which is just below the toxic level. The farther from the struts 13 the tissue to be treated is located, the lower the concentration of the biologically active material delivered to the tissue becomes. However, the area between line 18 and line 19 has the concentration level at or higher than Cmin. A concentration of the biologically active material in the area outside line 19 is below Cmin.
Also, FIGS. 2A and 2B clearly show that there are gaps between each strut 13 wherein the vessel wall to be treated does not receive sufficient biologically active material to have Cmin. The areas within line 19, i.e., having concentrations above Cmin, may be increased in size to include more area of the vessel wall 12 to be treated, if the amount of the biologically active material on the struts 13 is increased. However, by doing so, the concentration of the biologically active material in the area adjacent to the struts 13 may exceed the toxic level. Accordingly, there is a need for a medical device comprising a plurality of struts that can achieve the biologically active material concentration that is above Cmin and below toxic levels throughout the tissue.
Also, generally with existing coated medical devices, the coating is uniformly applied along the entire length of the device or surface of the device. For example, conventional coated stents are coated uniformly along the entire length of the surface of the device. The biologically active material-concentration-profile along the length of the coated surface may be in the shape of a bell-curve, wherein the concentration of the biologically active material released at the middle of the surface is greater than the concentration of the biologically active material released at the ends of the coated surface. This uneven concentration-profile along the length of the coated surface may lead to the application of an inadequate or sub-optimal dosage of the biologically active material to the body tissue located at the ends of the coated surface. It is possible that such uneven local concentration of the biologically active material along the length of the coated surface of the medical device may lead to undesired effects. For example, in the case of a biologically active material-coated stent used to prevent or treat restenosis, if the amount of biologically active material delivered to the tissue located at the ends of the stent is sub-optimal, it is possible that restenosis may occur in such tissue. In fact, recent data show that restenosis occurs at the edges of the stents about five times more often than at the middle portion of stents, i.e., the “edge effect”. The “edge effect” may be caused by the lesser concentration of biological active material that is present in body tissue in proximity to the edges of the stent.
The biologically active material dosage at the tissue located at the ends of the coated surface of the medical device can be increased if the concentration or amount of the biologically active material is increased along the entire length of the surface. However, by increasing the concentration or amount of biologically active material released along the entire surface, the dosage delivered to tissue located at the middle of the surface may be too great or even at toxic levels. Thus, there is a need for a medical device that can realize a more uniform concentration-profile for biologically active material along the entire length of a coated surface of a medical device and avoid the possibility of undesired effects accompanied by an uneven biologically active material concentration-profile.
Moreover, medical devices wherein a biologically active material is uniformly coated on the entire outer surface of the medical devices that is exposed to body tissue are generally used to deliver such biologically active material to specific parts of such body tissue. For instance, such devices are used to treat lesions in body lumen. However, because the entire outer surface of the device contains the biologically active material, this biologically active material will be delivered to healthy body tissue in addition to the lesion. Treatment of healthy tissue with the biologically active material is not only unnecessary but maybe harmful. Accordingly, there is a need for a medical device that can realize an asymmetry release-profile of biologically active material to deliver such material to only a limited region of the body tissue that requires the biologically active material.
Also, the pressure or stress that the stent exerts against the surrounding tissue is concentrated at the edges of the stent. Such concentrated stress may also contribute to the “edge effect”. Therefore, to reduce the “edge effect,” there is a need for a stent having a structure wherein the stress exerted against the body tissue in proximity to the edges of the stent is reduced and such body tissue is exposed to a greater amount of biologically active material.
Furthermore, when a balloon and a balloon expandable stent disposed on the balloon are expanded, the ends of the stent generally do not extend to the ends of the balloon, i.e., the ends of the stent do not cover the entire balloon's length. Thus, the balloon inflates beyond the margins or ends of the stents, and the portions of the balloon beyond the stents' ends directly contact the patient's lumen wall. Such direct contact with the balloon may cause a tissue injury in the patient's lumen wall. Also, to reduce such potential injury by using a balloon having a length which is matched exactly to a stent length is impractical because: (1) it is difficult to align the stent with the balloon during crimping; (2) both stent and balloon are manufactured within a small but finite tolerance that provides a range of component sizes; and (3) stents will be shortened during expansion. Therefore, there is a need for a stent having structure to reduce such potential injury caused by the ends or edges of the balloon.